SIRT1, metabolism and cancer.

John R.P. Knight, J. Milner

Research output: Contribution to journalReview articlepeer-review


SIRT1 impacts upon diverse cellular processes via its roles in the determination of chromatin structure, chromatin remodelling and gene expression. This review covers the recent discoveries linking SIRT1 with the regulation of mammalian metabolism and considers ways in which abnormal metabolism in disease may, in turn, impact upon SIRT1 because of SIRT1's functional dependency upon NAD. Diverse signalling pathways are integrated to regulate energy metabolism and homeostasis. Such pathways involve intracellular networks and mitochondria, and also intercellular signalling within and between tissues to co-ordinate adaptive metabolic responses within the organism as a whole. Here, we outline the recent studies exploring the regulatory links between SIRT1 and mitochondrial biogenesis, cellular redox and associated metabolic pathways, and angiogenesis/Notch signalling. These links are effected by the SIRT1-mediated deacetylation of transcriptional regulators and enzymes with key roles in metabolism. SIRT1 activity is directly coupled with homeostasis and metabolism. SIRT1 is also a metabolic sensor. It follows that disease-related metabolic abnormalities are likely to impinge upon SIRT1 functioning. Disease-related functions of SIRT1, in their turn, offer potential targets for the development of novel SIRT1-based therapies. In cancer, for example, the survival function of SIRT1 may reflect abnormal cancer metabolism and identifies SIRT1 as a target for anticancer therapy.

Original languageEnglish
Pages (from-to)68-75
Number of pages8
JournalCurrent opinion in oncology
Issue number1
Publication statusPublished - Jan 2012

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


Dive into the research topics of 'SIRT1, metabolism and cancer.'. Together they form a unique fingerprint.

Cite this